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Clinical Cardiology Jan 1991Over the past 30 years, knowledge of the natural history and effects of therapy in patients with hypertrophic cardiomyopathy has expanded greatly, but progress has been... (Review)
Review
Over the past 30 years, knowledge of the natural history and effects of therapy in patients with hypertrophic cardiomyopathy has expanded greatly, but progress has been hampered by its variable patterns of expression. Many but not all patients show symptomatic improvement with medical treatment. Chronic beta blockage does not appear to affect long-term survival, whereas results with calcium channel blockade by verapamil have been encouraging; however, they await confirmation, and verapamil may be hazardous in some patients with severe left ventricular (LV) outflow tract obstruction and elevated LV end-diastolic pressure. Reported beneficial effects of amiodarone on survival also require further study. Surgical therapy has become the treatment of choice for medically refractory patients with proven outflow tract obstruction. In several centers, the operative risk is low, and long-term follow-up demonstrates prolonged symptomatic relief. It is hoped that work currently underway will provide more definitive information on the long-term effects of the role of calcium channel blockers, antiarrhythmic medications, and the long-term effects of surgical therapy on survival of patients with this disorder.
Topics: Adrenergic beta-Antagonists; Adult; Calcium Channel Blockers; Cardiomyopathy, Hypertrophic; Child; Disopyramide; Humans; Infant; Prognosis
PubMed: 1673364
DOI: 10.1002/clc.4960140105 -
British Medical Journal (Clinical... Apr 1983
Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Aprindine; Benzeneacetamides; Disopyramide; Flecainide; Humans; Kinetics; Lidocaine; Mexiletine; Piperidines; Procainamide; Quinidine; Tocainide; Verapamil
PubMed: 6132656
DOI: 10.1136/bmj.286.6374.1332 -
British Journal of Anaesthesia May 1981The effect of disopyramide on neuromuscular transmission has been studied using the rat isolated phrenic nerve-diaphragm preparation. The response of the muscle to...
The effect of disopyramide on neuromuscular transmission has been studied using the rat isolated phrenic nerve-diaphragm preparation. The response of the muscle to indirect nerve stimulation was decreased in the presence of disopyramide 5.6 x 10(-6) mol litre-1 (P less than 0.05), total blockade occurring at 5.6 x 10(-4) mol litre-1. Marked augmentation of the response to direct muscle stimulation was recorded in the presence of disopyramide 1.8 x 10(-4)-5.6 x 10(-4) mol litre-1. Disopyramide 5.6 x 10(-6) mol litre-1 caused a leftward shift of the log concentration response for tubocurarine and decreased the antagonist effect of neostigmine.
Topics: Animals; Disopyramide; Dose-Response Relationship, Drug; Drug Synergism; In Vitro Techniques; Neostigmine; Neuromuscular Junction; Pyridines; Rats; Synaptic Transmission; Tubocurarine
PubMed: 6263303
DOI: 10.1093/bja/53.5.495 -
Journal of the American College of... Apr 2005In this study we assessed the long-term efficacy and safety of disopyramide for patients with obstructive hypertrophic cardiomyopathy (HCM).
OBJECTIVES
In this study we assessed the long-term efficacy and safety of disopyramide for patients with obstructive hypertrophic cardiomyopathy (HCM).
BACKGROUND
It has been reported that disopyramide may reduce left ventricular outflow gradient and improve symptoms in patients with HCM. However, long-term efficacy and safety of disopyramide has not been shown in a large cohort.
METHODS
Clinical and echocardiographic data were evaluated in 118 obstructive HCM patients treated with disopyramide at 4 HCM treatment centers. Mortality in the disopyramide-treated patients was compared with 373 obstructive HCM patients not treated with disopyramide.
RESULTS
Patients were followed with disopyramide for 3.1 +/- 2.6 years; dose 432 +/- 181 mg/day (97% also received beta-blockers). Seventy-eight patients (66%) were maintained with disopyramide without the necessity for major non-pharmacologic intervention with surgical myectomy, alcohol ablation, or pacing; outflow gradient at rest decreased from 75 +/- 33 to 40 +/- 32 mm Hg (p < 0.0001) and mean New York Heart Association functional class from 2.3 +/- 0.7 to 1.7 +/- 0.6 (p < 0.0001). Forty other patients (34%) could not be satisfactorily managed with disopyramide and required major invasive interventions because of inadequate symptom and gradient control or vagolytic side effects. All-cause annual cardiac death rate between disopyramide and non-disopyramide-treated patients did not differ significantly, 1.4% versus 2.6%/year (p = 0.07). There was also no difference in sudden death rate, 1.0%/year versus 1.8%/year (p = 0.08).
CONCLUSIONS
Two-thirds of obstructed HCM patients treated with disopyramide could be managed medically with amelioration of symptoms and about 50% reduction in subaortic gradient over >/=3 years. Disopyramide therapy does not appear to be proarrhythmic in HCM and should be considered before proceeding to surgical myectomy or alternate strategies.
Topics: Administration, Oral; Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Cardiomyopathy, Hypertrophic; Death, Sudden, Cardiac; Disopyramide; Echocardiography; Female; Humans; Male; Middle Aged; Myocardial Contraction; Safety; Treatment Outcome
PubMed: 15837258
DOI: 10.1016/j.jacc.2005.01.012 -
Advances in Medicine 2014Hypertrophic cardiomyopathy (HCM) is one of the more common hereditary cardiac conditions. According to presence or absence of outflow obstruction at rest or with... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is one of the more common hereditary cardiac conditions. According to presence or absence of outflow obstruction at rest or with provocation, a more common (about 60-70%) obstructive type of the disease (HOCM) has to be distinguished from the less common (30-40%) nonobstructive phenotype (HNCM). Symptoms include exercise limitation due to dyspnea, angina pectoris, palpitations, or dizziness; occasionally syncope or sudden cardiac death occurs. Correct diagnosis and risk stratification with respect to prophylactic ICD implantation are essential in HCM patient management. Drug therapy in symptomatic patients can be characterized as treatment of heart failure with preserved ejection fraction (HFpEF) in HNCM, while symptoms and the obstructive gradient in HOCM can be addressed with beta-blockers, disopyramide, or verapamil. After a short overview on etiology, natural history, and diagnostics in hypertrophic cardiomyopathy, this paper reviews the current treatment options for HOCM with a special focus on percutaneous septal ablation. Literature data and the own series of about 600 cases are discussed, suggesting a largely comparable outcome with respect to procedural mortality, clinical efficacy, and long-term outcome.
PubMed: 26556411
DOI: 10.1155/2014/464851 -
Journal of the American College of... Mar 1989The efficacy and tolerance of disopyramide and mexiletine used alone and in combination were studied in 21 patients with frequent (greater than or equal to 30/h)...
The efficacy and tolerance of disopyramide and mexiletine used alone and in combination were studied in 21 patients with frequent (greater than or equal to 30/h) ventricular premature complexes. Ambulatory electrocardiographic monitoring was performed at baseline and during therapy with disopyramide alone, mexiletine alone and a combination of disopyramide and mexiletine. During single drug therapy, the dose of disopyramide was 602 +/- 152 mg/day and that of mexiletine was 738 +/- 144 mg/day. During combination therapy with smaller doses of disopyramide (524 +/- 134 mg/day) and mexiletine (652 +/- 146 mg/day), no patient had side effects. At baseline before therapy, the mean number of ventricular premature complexes per hour, was 608 +/- 757, of couplets per hour was 22.4 +/- 45.8 and of episodes of nonsustained ventricular tachycardia/24 h was 219.7 +/- 758.2. The mean number of ventricular premature complexes per hour was reduced to 156 +/- 217 with disopyramide alone, 188 +/- 298 with mexiletine alone and 76 +/- 144 with combination therapy (p less than 0.05 for combination therapy versus disopyramide or mexiletine alone; p = NS for disopyramide versus mexiletine). Individually, an effective regimen (greater than 83% reduction in ventricular premature complexes and abolition of nonsustained ventricular tachycardia) was found in 5 (24%) of 21 patients during therapy with disopyramide alone, in 3 (14%) receiving mexiletine alone and in 13 (62%) receiving combination therapy (p less than 0.05 for combination therapy versus disopyramide or mexiletine; p = NS for disopyramide versus mexiletine). Thus, the antiarrhythmic effects of disopyramide and mexiletine are additive.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Disopyramide; Drug Therapy, Combination; Electrocardiography; Female; Heart Ventricles; Humans; Male; Mexiletine; Middle Aged; Monitoring, Physiologic; Tachycardia
PubMed: 2918173
DOI: 10.1016/0735-1097(89)90608-6 -
Frontiers in Cardiovascular Medicine 2022Brugada syndrome (BrS) is associated with ventricular tachyarrhythmias. However, the presence of electrical strom (ES) and its management still debated.
BACKGROUND
Brugada syndrome (BrS) is associated with ventricular tachyarrhythmias. However, the presence of electrical strom (ES) and its management still debated.
OBJECTIVES
We present the outcome and management of 44 BrS patients suffering from ES.
METHODS
A systematic literature review and pooled analysis Through database review including PubMed, Web of Science, Cochrane Libary and Cinahl studies were analyzed. Evidence from 7 reports of 808 BrS patients was identified.
RESULTS
The mean age of patients suffering from ES was 34 ± 9.5 months (94.7% males, 65.8% spontaneous BrS type I). Using electrophysiological study ventricular tachycardia/ventricular fibrillation were inducible in 12/23 (52.2%). Recurrence of ES was documented in 6.1%. Death from ES was 8.2% after a follow-up of 83.5 ± 53.4. In up to 27 ES resolved without treatment. External shock was required in 35.6%, internal ICD shock in 13.3%, Overdrive pacing, left cardiac sympathetic block and atropin in 2.2%. Short-term antiarrhythmic management was as the following: Isopreterenol or Isopreterenol in combination with quinidine 35.5%, orciprenaline in 2.2%, quinidine 2.2%, disopyramide 2.2% or denopamide 2.2%. However, lidocaine, magensium sulfate, mexiletine and propanolol failed to control ES.
CONCLUSION
Although ES is rare in BrS, this entity challenges physicians. Despite its high mortality rate, spontaneous termination is possible. Short-term management using Isoproterenol and/or quinidine might be safe. Prospective studies on management of ES are warranted.
PubMed: 36386327
DOI: 10.3389/fcvm.2022.981715 -
International Heart Journal 2011The combined effects of disopyramide (DP) and erythromycin (EM) on ventricular repolarization and the inciden-ces of ventricular premature contractions (VPCs) and... (Comparative Study)
Comparative Study
The combined effects of disopyramide (DP) and erythromycin (EM) on ventricular repolarization and the inciden-ces of ventricular premature contractions (VPCs) and torsades de pointes (TdP) were investigated in 12 anesthetized dogs with complete atrioventricular block. Monophasic action potentials (MAPs) were measured from the left and right ventricular (LV and RV) endocardium. The right or left ventricle was paced at a cycle length of 750-1000 msec. Dogs were divided into 2 groups and given either intravenous DP at 3 mg/kg and then intravenous EM at 50 mg/kg (group 1, n = 8), or intravenous EM at 50 mg/kg and then intravenous DP at 3 mg/kg (group 2, n = 4). MAP duration at 90% repolarization (MAPD(90)) was measured before drug administration (baseline) and again after administration of each drug. RV MAPD(90) and LV MAPD(90) increased significantly (P < 0.02) after administration of each drug in group 1 (RV MAPD(90): from 247.0 ± 36.3 [baseline] to 283.5 ± 38.3 to 321.8 ± 56.7; LV MAPD(90): from 262.6 ± 49.1 (baseline) to 296.1 ± 58.8 to 351.0 ± 80.6). Early afterdepolarizations developed in 2 group 1 dogs after administration of DP and in 4 additional dogs after administration of EM. Frequent VPCs occurred in 1 dog after administration of DP and in 2 additional dogs after administration of EM, and TdP and ventricular tachycardias developed in 2 of the 3 dogs after administration of EM. Similar trends occurred in group 2. These results indicate a potentially fatal interaction between DP and EM administered in clinically relevant doses.
Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Atrioventricular Block; Disease Models, Animal; Disopyramide; Dogs; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electrocardiography; Erythromycin; Heart Conduction System; Prognosis; Protein Synthesis Inhibitors; Ventricular Function
PubMed: 22188715
DOI: 10.1536/ihj.52.393 -
PloS One 2017Short QT syndrome (SQTS) is an inherited disorder associated with abnormally abbreviated QT intervals and an increased incidence of atrial and ventricular arrhythmias....
AIMS
Short QT syndrome (SQTS) is an inherited disorder associated with abnormally abbreviated QT intervals and an increased incidence of atrial and ventricular arrhythmias. SQT1 variant (linked to the rapid delayed rectifier potassium channel current, IKr) of SQTS, results from an inactivation-attenuated, gain-of-function mutation (N588K) in the KCNH2-encoded potassium channels. Pro-arrhythmogenic effects of SQT1 have been well characterized, but less is known about the possible pharmacological antiarrhythmic treatment of SQT1. Therefore, this study aimed to assess the potential effects of E-4031, disopyramide and quinidine on SQT1 using a mathematical model of human ventricular electrophysiology.
METHODS
The ten Tusscher et al. biophysically detailed model of the human ventricular action potential (AP) was modified to incorporate IKr Markov chain (MC) formulations based on experimental data of the kinetics of the N588K mutation of the KCNH2-encoded subunit of the IKr channels. The modified ventricular cell model was then integrated into one-dimensional (1D) strand, 2D regular and realistic tissues with transmural heterogeneities. The channel-blocking effect of the drugs on ion currents in healthy and SQT1 cells was modeled using half-maximal inhibitory concentration (IC50) and Hill coefficient (nH) values from literatures. Effects of drugs on cell AP duration (APD), effective refractory period (ERP) and pseudo-ECG traces were calculated. Effects of drugs on the ventricular temporal and spatial vulnerability to re-entrant excitation waves were measured. Re-entry was simulated in both 2D regular and realistic ventricular tissue.
RESULTS
At the single cell level, the drugs E-4031 and disopyramide had hardly noticeable effects on the ventricular cell APD at 90% repolarization (APD90), whereas quinidine caused a significant prolongation of APD90. Quinidine prolonged and decreased the maximal transmural AP heterogeneity (δV); this led to the decreased transmural heterogeneity of APD across the 1D strand. Quinidine caused QT prolongation and a decrease in the T-wave amplitude, and increased ERP and decreased temporal susceptibility of the tissue to the initiation of re-entry and increased the minimum substrate size necessary to prevent re-entry in the 2D regular model, and further terminated re-entrant waves in the 2D realistic model. Quinidine exhibited significantly better therapeutic effects on SQT1 than E-4031 and disopyramide.
CONCLUSIONS
The simulated pharmacological actions of quinidine exhibited antiarrhythmic effects on SQT1. This study substantiates a causal link between quinidine and QT interval prolongation in SQT1 and suggests that quinidine may be a potential pharmacological agent for treating SQT1 patients.
Topics: Action Potentials; Arrhythmias, Cardiac; Cell Line; Disopyramide; ERG1 Potassium Channel; Electrocardiography; Heart Ventricles; Humans; Models, Biological; Piperidines; Polymorphism, Single Nucleotide; Pyridines; Quinidine
PubMed: 28632743
DOI: 10.1371/journal.pone.0179515 -
Journal of the American College of... May 2019The short QT syndrome (SQTS) is an inherited arrhythmogenic syndrome characterized by abnormal ion channel function, life-threatening arrhythmias, and sudden cardiac...
BACKGROUND
The short QT syndrome (SQTS) is an inherited arrhythmogenic syndrome characterized by abnormal ion channel function, life-threatening arrhythmias, and sudden cardiac death.
OBJECTIVES
The purpose of this study was to establish a patient-specific human-induced pluripotent stem cell (hiPSC) model of the SQTS, and to provide mechanistic insights into its pathophysiology and therapy.
METHODS
Patient-specific hiPSCs were generated from a symptomatic SQTS patient carrying the N588K mutation in the KCNH2 gene, differentiated into cardiomyocytes, and compared with healthy and isogenic (established by CRISPR/Cas9-based mutation correction) control hiPSC-derived cardiomyocytes (hiPSC-CMs). Patch-clamp was used to evaluate action-potential (AP) and I current properties at the cellular level. Conduction and arrhythmogenesis were studied at the tissue level using confluent 2-dimensional hiPSC-derived cardiac cell sheets (hiPSC-CCSs) and optical mapping.
RESULTS
Intracellular recordings demonstrated shortened action-potential duration (APD) and abbreviated refractory period in the SQTS-hiPSC-CMs. Similarly, voltage- and AP-clamp recordings revealed increased I current density due to attenuated inactivation, primarily in the AP plateau phase. Optical mapping of the SQTS-hiPSC-CCSs revealed shortened APD, impaired APD-rate adaptation, abbreviated wavelength of excitation, and increased inducibility of sustained spiral waves. Phase-mapping analysis revealed accelerated and stabilized rotors manifested by increased rotor rotation frequency, increased rotor curvature, decreased core meandering, and increased rotor complexity. Application of quinidine and disopyramide, but not sotalol, normalized APD and suppressed arrhythmia induction.
CONCLUSIONS
A novel hiPSC-based model of the SQTS was established at both the cellular and tissue levels. This model recapitulated the disease phenotype in the culture dish and provided important mechanistic insights into arrhythmia mechanisms in the SQTS and its treatment.
Topics: Action Potentials; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cells, Cultured; ERG1 Potassium Channel; Humans; Induced Pluripotent Stem Cells; Mutation; Myocytes, Cardiac; Patch-Clamp Techniques; Patient-Specific Modeling
PubMed: 31072576
DOI: 10.1016/j.jacc.2019.02.055